Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats

A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. 

We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. 

Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice.

Milnacipran dose dependently (5–40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. 

Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. 

Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran

Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. 

Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. 

Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. 

These results support that SNRIs may have a potential use in alcoholism treatment.

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Request Reprint E-Mail:  mickael.naassila@u-picardie.fr   

Strain-specific vulnerability to alcohol exposure in utero via hippocampal parent-of-origin expression of deiodinase-III

Prenatal exposure to alcohol is thought to be the most prevalent nongenetic cause of a wide range of neurodevelopmental deficits. 

Insufficient thyroid hormone levels are one mechanism that hampers development of the alcohol-exposed brain, and we hypothesized that altered dosage of the imprinted thyroid hormone-inactivating gene deiodinase-III (Dio3) is responsible. 

To follow parent-of-origin allelic expression of Dio3 in the fetal and adult offspring of alcohol-consuming and control dams, we reciprocally crossed 2 polymorphic rat strains. 

In the frontal cortex, prenatal alcohol exposure altered imprinting patterns and total expression of Dio3 in the fetus and produced a permanent hypothyroid milieu in the adult. In the hippocampus, alcohol affected the paternal and total expression of Dio3 in the fetus and in the adult male, where thyroid hormone levels were concomitantly increased. 

Hippocampus-dependent behavioral deficits were identified exclusively in males, suggesting they are dependent on aberrant allelic Dio3 expression. None of these effects were observed in offspring of the reciprocal cross. 

Thus, genetic background and sex modify vulnerability to prenatal alcohol via brain region-specific expression of Dio3. 

This finding implies that phenotypic heterogeneity in human fetal alcohol spectrum disorder can be linked to genetic vulnerability in affected brain regions.

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Request Reprint E-Mail:   e-redei@northwestern.edu

Does Active Substance Use at Housing Entry Impair Outcomes in Supported Housing for Chronically Homeless Persons?

Recent clinical and policy trends have favored low-demand housing (provision of housing not contingent on alcohol and drug abstinence) in assisting chronically homeless people. 

This study compared housing, clinical, and service use outcomes of participants with high levels of substance use at time of housing entry and those who reported no substance use.

Participants in the outcome evaluation of the 11-site Collaborative Initiative on Chronic Homelessness (N=756), who were housed within 12 months of program entry and received an assessment at time of housing and at least one follow-up (N=694, 92%), were classified as either high-frequency substance users (>15 days of using alcohol or >15 days of using marijuana or any other illicit drugs in the past 30 days; N=120, 16%) or abstainers (no days of use; N=290, 38%) on entry into supported community housing. An intermediate group reporting from one to 15 days of use (N=284, 38%) was excluded from the analysis. Mixed-model multivariate regression adjusted outcome findings for baseline group differences.

During a 24-month follow-up, the number of days housed increased dramatically for both groups, with no significant differences. High-frequency substance users maintained higher, though declining, rates of substance use throughout follow-up compared with abstainers. High-frequency users continued to have more frequent or more severe psychiatric symptoms than the abstainers. Total health costs declined for both groups over time.

Active-use substance users were successfully housed on the basis of a low-demand model. Compared with abstainers, users maintained the higher rates of substance use and poorer mental health outcomes that were observed at housing entry but without relative worsening.


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Request Reprint E-Mail:   ellen.edens@va.gov

News Release - FTC Seeks Public Comment on Proposed Information Requests to Alcohol Beverage Manufacturers

The Federal Trade Commission plans to begin a study of the self-regulatory efforts of the alcoholic beverage industry.  This will serve as the basis for the FTC’s fourth major report on the effectiveness of voluntary industry guidelines for reducing advertising and marketing to underage audiences by beer, wine, and distilled spirits manufacturers.  The first report was published in 1999.

The FTC is seeking clearance from the Office of Management and Budget (OMB) to collect information from the alcohol companies, which is the first step toward conducting the study.  It has published a Federal Register notice seeking public comment on the proposed collection of data from these companies.  The topics the FTC seeks comment on include:

• the companies’ compliance with voluntary advertising placement provisions, sales, and marketing expenditures;
• the status of third-party review of complaints regarding compliance with voluntary advertising codes; and
• alcohol industry data-collection practices.  > > > >  Read More

Scientific publications on Alcohol Marketing

Research topics:

• Research on the Impact of Alcohol Marketing
  
• Research on Effectiveness Policies to Regulate Alcohol Marketing
  
• Research on Alcohol Marketing and the Alcohol Industry
  
• Research on the Impact of Counter-Advertising

New Report: The Seven Key Messages of the Alcohol Industry

A number of European health organizations have concluded that the influence of the alcohol industry on the policy of national and European governments is very effective. The result of this is that essential (evidence based) policy changes are held of and the dramatic damages caused by alcohol are not contained. The succes of the industry, according to these organizations, means that many people die unnecessarily due to alcohol use and that costs for society are kept needlessly high.  > > > >  Read More

Relationship between alcohol consumption and myocardial infarction among ageing men using a marginal structural model

Studies on the association between alcohol consumption and myocardial infarction (MI) have typically used baseline data on alcohol consumption and potential confounders. 

This study aimed at investigating the association between alcohol consumption and MI considering time-varying alcohol consumption and time-varying confounders.

 

Data were available for 1030 males participating in the Kuopio Ischaemic Heart Disease Risk Factor Study (Finland). Baseline data for the present study were collected in 1991–93. MIs were ascertained from national registries until December 2005. Alcohol consumption was categorized into four groups. Data were analysed using conventional discrete-time hazard and marginal structural models (MSMs). Time-invariant covariates were age, working status, diabetes and cigarette-years. Time-varying covariates in the MSM were prior alcohol consumption, smoking, history of cardiovascular diseases, body mass index, high-density lipoprotein cholesterol, systolic blood pressure, insulin and fibrinogen.  

An insignificant increase of MI risk among the heaviest alcohol consumers (≥168 g week⁻¹) compared with the reference group (12–83 g week⁻¹) was observed when using a conventional model including baseline alcohol consumption and confounders measured prior to baseline [relative risk (RR) = 1.20, 95% confidence interval (95% CI) = 0.68–2.12]. When using a conventional model with time-varying alcohol consumption and adjusting for prior confounders, an increased risk of MI among the heaviest alcohol consumers was revealed (RR = 1.71, 95% CI = 1.03–2.85). There was also a trend towards increased risk among the heaviest consumers using the MSM (RR = 1.59, 95% CI = 0.93–2.72). 

Our findings suggest that standard methods using only baseline data on alcohol consumption and confounders may lead to biased estimates on the association between alcohol consumption and MI. 

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Request Reprint E-Mail:  jenni.ilomaki@uef.fi  

Welcome to the Psychotherapeutic Medications 2011: What Every Counselor Should Know

If you are an addiction and/or a mental health specialist and do not have medical training, this site is for you!
The Rx Database www.findrxinformation.org is designed as a "desk-top reference" of medications commonly prescribed in the treatment of persons with alcohol, drug and mental health conditions.

This searchable database offers up-to-date information on generic and brand name medications. It is intended to provide a basic understanding of medication dose, frequency, side effects, emergency conditions, abuse potential, cautions and considerations for pregnant women.


Search Database

A Case–Control Study of Severe Physical Abuse of Older Adults

To characterize the severity and outcome of traumatic injuries suffered by victims of elder abuse, describe the characteristics of the perpetrators, and identify risk factors associated with severe traumatic elder abuse.

Case–control study.

Two Level I trauma units in the greater Chicago, Illinois, metropolitan area.

Forty-one cases of elder abuse resulting in severe traumatic injury were identified between 1999 and 2006. Controls were randomly selected from the list of elderly patients in the trauma registry (N=123).

Elder abuse was defined according to the Illinois Elder Abuse and Neglect Act.

In this study, 85% of the perpetrators were family members or intimate partners. In the final multivariable logistic regression model, victims of severe traumatic elder abuse were more likely to be female, to have a neurological or mental disorder, and to abuse drugs or alcohol.


Read Full Abstract 

Request Reprint E-Mail:  lfriedman@tspri.org  

This is the first clinical case–control study detailing clinical outcomes and evaluating risk factors of persons suffering severe physical abuse. Of elderly trauma victims, those who are physically abused have more-severe injuries than their nonabused counterparts. More research is needed to better evaluate risk factors of physical abuse and effective interventions.

News Release - Recent trends in alcohol sales revealed

A report published today by NHS Health Scotland, reveals that over the past 15 years annual alcohol sales in Scotland have increased by 11% - equivalent to over one litre of pure alcohol per adult per year.

This was driven by a 53% increase in the amount of alcohol being sold through off-sales at a time when prices increased more slowly in off-sales (supermarkets and other licensed shops) than on-sales (pubs, restaurants and clubs). Sales of wine in Scotland have more than doubled since 1994 and adults in Scotland now buy more wine per head than their counterparts in England and Wales. Annual sales of spirits in Scotland were consistently almost double those in England and Wales during this period.  > > > >   Read More

A Discrete Alcohol Pocket Involved in GIRK Channel Activation

Ethanol modifies neural activity in the brain by modulating ion channels. Ethanol activates G protein-gated inwardly rectifying K⁺ channels, but the molecular mechanism is not well understood. 

Here, we used a crystal structure of a mouse inward rectifier containing a bound alcohol and structure-based mutagenesis to probe a putative alcohol-binding pocket located in the cytoplasmic domains of GIRK channels. 

Substitutions with bulkier side-chains in the alcohol-binding pocket reduced or eliminated activation by alcohols. By contrast, alcohols inhibited constitutively open channels, such as IRK1 or GIRK2 that binds PIP₂ strongly. 

Mutations in the hydrophobic alcohol-binding pocket of these channels had no effect on alcohol-dependent inhibition, suggesting an alternate site is involved in inhibition. 

Comparison of high-resolution structures of inwardly rectifying K⁺ channels suggests a model for activation of GIRK channels utilizing this hydrophobic alcohol-binding pocket. 

These results provide a tool for developing therapeutic compounds that could mitigate the effects of alcohol.

Read Full Article    (PDF)

News Release - Salk scientists crack molecular code regulating neuronal excitability

A key question in protein biochemistry is how proteins recognize "correct" interaction partners in a sea of cellular factors. Nowhere is that more critical to know than in the brain, where interactions governing channel protein activity can alter an organism's behavior. A team of biologists at the Salk Institute for Biological Studies has recently deciphered a molecular code that regulates availability of a brain channel that modulates neuronal excitability, a discovery that might aid efforts to treat drug addiction and mental disorders. 

In the this week's Online Early Edition of the Proceedings of the National Academy of Sciences, Paul Slesinger, Ph.D., Associate Professor in the Clayton Foundation Laboratories for Peptide Biology, and colleagues detail how a regulatory factor called SNX27 distinguishes a brain channel protein called GIRK (short for G-protein-coupled inwardly rectifying potassium channels) from structurally similar proteins and then targets it for destruction.

  

That work extends the group's 2007 study showing that when SNX27 proteins capture GIRK channels, reducing the number of channels at their rightful destination, the cell membrane. "We were curious about what determined the selectivity of this interaction," says Slesinger. "We knew that SNX27 interacted with a structural motif found on GIRK channels but many channel proteins display a similar motif. We wanted to know what allowed SNX27 to specifically choose GIRK channels." 

Knowing this is critical because of the connection of GIRK channels to substance abuse. Slesinger and others have shown that alcohol or club drugs linked to sexual assault (GHB) affects GIRK channel function in the brain. Loss-of-inhibition behaviors associated with abuse of these substances result from the fact that GIRK channels allow potassium ions to leak out of a stimulated neuron, thereby dampening a cell's excitability.

> > > >   Read More

Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27

G protein-gated inwardly rectifyingpotassium (GIRK) channels are important gatekeepers of neuronal excitability.  

The surface expression of neuronal GIRK channels is regulated by the psychostimulant-sensitive sortingnexin 27 (SNX27) protein through a class I (-X-Ser/Thr-X-Φ, where X is any residue and Φ is a hydrophobic amino acid) PDZ-binding interaction.
 

The G protein-insensitive inward rectifier channel (IRK1) contains the same class I PDZ-binding motif but associates with a different synaptic PDZ protein, postsynaptic density protein 95 (PSD95).  

The mechanism by which SNX27 and PSD95 discriminate these channels was previously unclear. Using high-resolution structures coupled with biochemical and functional analyses, we identified key amino acids upstream of the channel's canonical PDZ-binding motif that associate electrostatically with a unique structural pocket in the SNX27-PDZ domain.

Changing specific charged residues in the channel's carboxyl terminus or in the PDZ domain converts theselective association and functional regulation by SNX27. 

Elucidation of this unique interaction site between ion channels and PDZ-containing proteins could provide a therapeutic target for treating brain diseases. 

Read Full Abstract 

Request Reprint E-Mail:  slesinger@salk.edu    

Drink-Drive limit to remain 80mg

The legal drink-drive limit will remain at 80mg per 100ml of blood, the transport secretary Philip Hammond has announced. A Government press release said the focus would instead be on "improving enforcement and education to tackle the drink and drug drivers who put lives at risk."   > > > >  Read More

Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome

Several correlated phenotypes, alcohol dependence, major depressive syndrome, and an endophenotype of electrophysiological measurements, event-related oscillations (EROs), have demonstrated linkage on the long arm of chromosome 7. 

Recently, we reported both linkage and association between polymorphisms in the gene encoding the muscarinic acetylcholine receptor M2 (CHRM2) and EROs.

In this study, we evaluated whether genetic variation in the CHRM2 gene is also a risk factor for the correlated clinical characteristics of alcoholism and depression. 

The CHRM2 gene contains a single coding exon and a large 5′ untranslated region encoded by multiple exons that can be alternatively spliced. Families were recruited through an alcohol dependent proband, and multiplex pedigrees were selected for genetic analyses. We examined 11 single nucleotide polymorphisms (SNPs) spanning the CHRM2 gene in these families. 

Using the UNPHASED pedigree disequilibrium test (PDTPHASE), three SNPs (one in intron 4 and two in intron 5) showed highly significant association with alcoholism (P=0.004–0.007). Two SNPs (both in intron 4) were significantly associated with major depressive syndrome (P=0.004 and 0.017). 

Haplotype analyses revealed that the most common haplotype (>40% frequency), T–T–T (rs1824024–rs2061174–rs324650), was under-transmitted to affected individuals with alcohol dependence and major depressive syndrome. Different complementary haplotypes were over-transmitted in alcohol dependent and depressed individuals. 

These findings provide strong evidence that variants within or close to the CHRM2 locus influence risk for two common psychiatric disorders. 


Read Full Article    (PDF)

News Release - Government crackdown on drink and drug driving

Improved testing equipment to detect drink and drug drivers will be given the green light and key changes made to streamline enforcement of both offences.

The Government will also examine the case for a new specific drug driving offence – alongside the existing one – which would remove the need for the police to prove impairment on a case-by-case basis where a specified drug has been detected.

The measures are set out in the Government’s response to the North Report on Drink and Drug Driving, which was published last year.

The prescribed alcohol limit for driving will not be changed, with the focus instead on improving enforcement and education to tackle the drink and drug drivers who put lives at risk. > > > >  Read More

Using taxes to curb drinking: A report card on the Australian government's alcopops tax

In 2008, the Australian government introduced an ‘alcopops tax’ on spirit-based ready-to-drink (RTD) beverages to reduce alcohol consumption and particularly binge drinking by young people.

Data regarding sales of alcoholic beverages in Australia from 2004 to 2009 were used to examine the possible effects of the alcopops tax. In addition, population data were used to calculate and examine per capita consumption.

Various measures of consumption of wine-based RTDs, spirits, cider, wine and beer remained fairly stable or increased annually from 2004 to 2009. Consumption of spirit-based RTDs increased annually from 2004 to 2007, but then decreased in 2008 and 2009. Per capita alcohol consumption in terms of pure alcohol increased annually from 11.52 litres in 2004 to a peak of 11.79 litres in 2007, but then dropped to 11.55 litres and 11.41 litres in 2008 and 2009, respectively.

Consumption of spirit-based RTDs dropped and consumption of other alcoholic beverages increased following the introduction of the tax. The increased consumption of other alcoholic beverages could be interpreted as indicating that RTD drinkers switched to purchasing spirits or wine-based RTDs or cider. However, those increases could also be interpreted as a continuation of long-term trends rather than a ‘substitution effect’. It is impossible to know how much of the changes were due to the tax, to the ‘global financial crisis’, to adaptive marketing by the alcohol industry, to the Government's national binge drinking strategy, to mass media coverage of these issues or to other factors.


Read Full Abstract 

Request Reprint E-Mail:   e.digiusto@unsw.edu.au 

News Release - Professor Marlatt’s Research Led to Increased Understanding of Addictive Behaviors

University of Washington College of Arts & Sciences learned yesterday that Professor G. Alan Marlatt, a clinical psychologist whose groundbreaking work in addictive behaviors spanned nearly four decades, passed away on Monday morning, March 14.
 
Marlatt’s research had a major impact on understanding the interaction between thoughts, emotions, and situations as predictors of addictive behaviors, such as substance abuse problems.
 
Marlatt was a full professor and director of the Addictive Behaviors Research Center at the University of Washington (UW). He joined the UW faculty in 1972 and founded the Addictive Behaviors Research Center within the department of Psychology a decade later. He has mentored hundreds of researchers and clinicians in the field of addictive behaviors.  > > > > Read More
“

Alcohol News - 12/2011

TheParliament.com (EU) - EU urged to put health warnings on beers and wines

A UK health expert has called for mandatory health warning information on alcohol drinks. Speaking in parliament on Thursday, Nick Sheron, however, cautioned against the "nasty, horrible" images on tobacco packaging.

Read more

Norway: Government has to accept alcohol advertising on TV

The EU Commission will not grant Norway a continued exemption from the implementation of the Audiovisual Media Services Directive. This means that the Norwegian government will have to accept TV advertising for alcoholic beverages in Norway when it is broadcast from another country.

Read more

BusinessWeek (Germany) - Drinking Behavior May Be Tied to Early Alcohol Use

Young adults are more likely to be heavy drinkers if they took their first drink of alcohol at an early age and also had to cope with stressful life events, a new study suggests.

Read more

Fox News - Heavy Drinking Linked to Increased Risk of Pancreatic Cancer

Smoking is one of the biggest risk factors when it comes to pancreatic cancer, and now it appears drinking is too.

Read more

New York Daily News - Hangovers only get worse as we get older, experts say; Processing alcohol gets tougher with age

While it may be hard to ignore the lure of St. Patrick's Day revelry, experts say you might want to think twice before hitting the Guinness like you might have in your younger years. Science shows that hangovers actually get worse with age, MSNBC.com reported.

Read more

BusinessWeek - Rat Study Sheds Light on How Alcohol Affects Young Brain

Based on the results of a new study conducted with rats, researchers say that kids who drink alcohol may have trouble with decision-making in adulthood.

Read more

ABC Online (Australia) - Aussie women among worst for alcohol impact

Australian men and women like to drink but an international study has found that for Australian women, the social and personal consequences of drinking are among the worst in the world.

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Sify - Parental monitoring 'decreases alcohol-related problems in young adults'

A new study suggests that those young adults whose parents monitor their social interactions may be less likely to display impulsive behavior traits and to have alcohol-related problems.

Read more

The Imperfect Parent - Teens from wealthy families more likely to drink

A recent UK study has shown that teens from wealthier families have a tendency to drink more alcohol than their peers from lower income families. The study was based on the responses of 5,837 thirteen year-olds who were involved in a long-term health study. For this part of the study, the teens’ families were divided into five different income brackets.

Read more

Independent (UK) - Government rules out lower drink-drive limit

Britain’s legal drink-drive limit will not be lowered, the Government said today, despite a recommendation by its own experts that it should be reduced.

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Times LIVE (South Africa) - Poverty fuelling drug and alcohol abuse

The widespread poverty and unemployment in South Africa is fuelling drug and alcohol abuse, Congress of SA Trade Unions general secretary Zwelinzima Vavi says.

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The Press Association (Scotland) - Government hits alcohol help target

A target to help address alcohol abuse has been reached ahead of schedule, according to the Scottish Government.

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NEWS.com.au (Australia) - Parents coud be fined under fresh booze law

VICTORIA will join New South Wales, Tasmania and Queensland by making it illegal for adults to give children alcohol in their homes without parental permission.

Read more

Lincoln Journal Star (USA) - Bill would end insanity defense in criminal cases involving drugs or alcohol

Lawmakers gave 40-2, first-round approval to his bill (LB100) Tuesday that would eliminate the criminal defense of "not responsible by reason of insanity" in situations in which a defendant was voluntarily intoxicated or high when a crime was committed.

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BBC News (Wales) - Alcohol Concern Cymru in Welsh assembly drink laws call

Alcohol campaigners are calling for the Welsh Assembly Government to be given the powers to set minimum prices for drink.

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NASDAQ (Peru) - Drugs And Alcohol Become Election Issues In Peru

With opponents breathing down his neck, presidential front- runner Alejandro Toledo has taken a blood test to show he is clean of any drug use, and says he has given up drinking hard liquor.

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This is London (UK) - Government deal with alcohol industry under fire again

The controversial public health agreement between the Government and the food and drink industries has come under fresh attack from leading health organisations, leaving major retailers as its main backers.

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Morning Advertiser (Scotland) - Diageo severs ties with Alcohol Focus Scotland group

Drinks giant Diageo has cut its ties with Scotland’s most prominent alcohol awareness charity after the group suggested alcohol policy should be similar to that on tobacco.

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Podcast - Worldwide alcohol trends

New and comprehensive study on the consumption of alcohol reveals worrying trends on alcohol use around the world. 

 

• Listen to this episode - duration 00:05:56 [mp3 3.5Mb] 
•  
•  Global status report on alcohol and health 2011